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Class antileprotic drugs

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Class antileprotic drugs

  1. 1. Dr. RAGHU PRASADA M S MBBS,MD ASSISTANT PROFESSOR DEPT. OF PHARMACOLOGY SSIMS & RC. 1
  2. 2. Leprosy is caused by a slow-growing type of bacteria called Mycobacterium leprae (M. leprae) Also known as Hansen's disease, after the scientist ho discovered M. leprae in 1873 It primarily affects the skin and the peripheral nerves Long Incubation period (3 – 5 years)
  3. 3. Sulfones – DAPSONE ( DDS)-DIAMINO DIPHENYL SULFONE Phenazine Derivative - CLOFAZIMINE Antitubercular Drugs - RIFAMPICIN, ETHIONAMIDE Antibiotics: OFLOXACIN, MOXIFLOXACIN, MINOCYCLINE AND CLARITHROMYCIN
  4. 4. The simplest, oldest, cheapest MOA: Leprostatic even at low concentration Chemically related to Sulfonamides – same mechanism – inhibition of incorporation of PABA into folic acid (folic acid synthase) Specificity to M leprae – affinity for folate synthase Activity: Used alone – resistance – MDT needed Resistance – Primary and Secondary (mutation of folate synthase – lower affinity) However, 100 mg/day – high MIC -500 times and continued to be effective to low and moderately resistant Bacilli (low % of resistant patient) Persisters. Also has antiprotozoal action (Falciparum and T. gondii)
  5. 5. Pharmacokinetics: Complete oral absorption and high distribution (less CNS penetration) Half life 24-36 Hrs, but cumulative 70% bound to plasma protein – concentrated in Skin, liver, muscle and kidney Acetylated and glucoronidated and sulfate conjugated – enterohepatic circulation ADRs: Generally Well tolerated drug Haemolytic anaemia (oxidizing property) - G-6-PD are more susceptible Gastric - intolerance, nausea, gastritis Methaemoglobinaemia, paresthesia, allergic rashes, FDE, phototoxicity, exfoliative dermatitis and hepatotoxicity etc.
  6. 6. Active against protozoa Combined with pyrimethamine alternative to sulfadoxine-pyrimethamine for P.falciparum and toxoplasma gondii infection Active against Pneumocystis jirovecii Also has anti-inflammatory property
  7. 7. Symptoms: Fever, malaise, lymph node enlargement, desquamation of skin, jaundice and anemia Starts after 4- 6 weeks of therapy, more common with MDT Management: stopping of Dapsone, corticosteroid therapy Dapsone contraindications: Severe anaemia and G-6- PD deficiency
  8. 8. Phenazine dye – antileprotic, anti-inflammatory and Bacteriostatic MOA: Interference with template function of DNA Alteration of membrane structure and transport Disruption of mitochondrial electron transport Monotherapy causes resistance in 1 – 3 years Dapsone resistants respond to Clofazimine Kinetics: absorbed orally (70%) and gets deposited in subcutaneous tissues – as crystals Half life – 70 days
  9. 9. ADRs: well tolerated Skin: Reddish-black discolouration of skin, discolouration of hair and body secretions Dryness of skin and troublesome itching, phototoxicity, conjunctival pigmentation GIT: Nausea, anorexia, abdominal pain and loose stool (early and late) – dreaded enteritis Contraindication: Early pregnancy, liver and kidney diseases
  10. 10. Rifampicin: Cidal. 99.99% killed in 3-7 days, skin symptoms regress within 2 months Included in MDT to shorten the duration of treatment and also to prevent resistance No toxic dose as single dose only Should not be used in ENL and Reversal phenomenon Ofloxacin: all fluoroquinolones except ciprofloxacin are active. Used as alternative to Rifampicin Minocycline: Lipophillic - enters M leprae. Less marked effect than Rifampicin
  11. 11. Anti leprotic and anti tubercular It is a fast acting drug than dapsone But it is more expensive and more toxic It is orally effective and it is administered daily Poorly tolerated –hepatotoxicity 250mg/day
  12. 12. Only macrolide with activity against M. leprae Less bactericidal than rifampin Monotherapy- 500mg daily/ 8wks- 99.9% killing Synergistic action with minocycline Used in alternative MDT regimen MINOCYCLINE High lipophilicity –penetrates into M.leprae 100mg/day Antileprotic activity rif>mino >Clari 8 wks treatment
  13. 13. The acute exacerbation which occurs during the course of leprosy is called as lepra reaction It occursin LL type- after starting with chemotherapy and intercurrent infections Jerish Hexheimer (Arthus) type reaction due to release of antigens from killed bacilli May be mild severe or life threatening ENL- erythema Nodosum Leprosum Treatment-clofazimine -200mg Dapsone temporary withdrawal Severe reaction- prednisone-40-60 mg.. Tapered in 2-3 months Thalidomide –alternative to prednisolone in ENL
  14. 14. TT and BL cases Manisfestation of delayed hypersensitivity to M.leprae antigens Cutaneous ulceration, multiple nerve involvement with tender nerves Treatment-Clofazimine/ corticosteroids
  15. 15. Lepromatous-LL Borderline –BL Borderline tubercular-BT Tuberculoid TT Conventional monotherapy MT-Dapsone 100-200m-/ 5/7 days in week TT-4-5 yrs LT- 8-12 yrs or life long
  16. 16. Tuberculoid Anaesthetic patch CMI-cell mediated immunity is normal Lepromin test is positive Bacilli rarely found in biopsy Prolonged remission with periodic exacerbations Lepromatous Diffuse skin and mucous membrane, nodules CMI is absent Lepromin test is negetive Skin and mucous membr biopsy +ve for bacilli Prognosis to anaesthesia of distal parts, atropy
  17. 17. Monotherapy - 1982 and since then MDT Elimination achieved in India in 2005 (prevalence rate ?) Leprosy classified as LL, BL, BB, BT and TT For operational purposes: Paucibacillary: few bacilli and non-infectious – TT and BT Multibacillary: large bacilli load and infectious – LL, BL and BB types Single lesion Paucibacillary: single lesion
  18. 18. MULTIBACILLARY RIFAMPIN-600mg OD/once per month Dapsone -100mg daily Clofazimine-300mg once/month 50mg-OD Duration -12 months PAUCIBACILLARY RIFAMPIN-600mg OD/once per month Dapsone -100mg daily 6 months
  19. 19. Alternative regimens Intermittent ROM Rifampin 600mg + Oflox 400mg + Minocycline 100 Once/month PBL 3-6months MBL 12-24 months Clofazimine 50mg + (any 2) 6months Ofoxacin 400mg Minocycline 100mg Clarithromycin 500mg RMMx regimen Moxiflox 400mg + minocycline 200mg Rifampin 600mg PBL- 6doses MBL-12 doses Clofazimine 50mg (any 1) 4 drug regimen Rifampin 600mg For 12wks is similar to standard MDT for 12 months Ofloxacin 400mg Minocycline 100mg Sparfloxacin 200mg 18 months Clarithromycin 500mg Minocycline 100mg
  20. 20. THANKYOU Download slides from Authorstream-raghuprasada Slideshare-raghuprasada Youtube-raghuprasada

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